The current FDA-approved drugs to treat post-traumatic stress disorder (PTSD) are often only minimally effective in clinical practice. One response is the frequent use of off-label drugs in the hope of improving the quality of life of patients impacted by PTSD. This approach often comes with adverse consequences for patients and with little improvement in their quality of life. But the treatment landscape for PTSD may change for the better with the emergence of a number of investigative agents. Join Drs. Joseph Goldberg and Roger McIntyre as they evaluate the value proposition of both current PTSD treatments and those in clinical trials.
Current and Emerging Treatments for PTSD in Women: An In-Depth Overview
Introduction
Post-traumatic stress disorder (PTSD) is a complex, multifaceted condition that significantly impacts the lives of many women, who are 2-3x more likely than men to develop PTSD after a serious or potentially life-threatening traumatic event. Despite the availability of treatment guidelines, many patients with PTSD are not being managed according to current recommendations, leading to suboptimal patient outcomes and significant impacts to quality of life. This summary explores the existing treatments, the challenges with guideline adherence, the importance of emerging therapies, and the need for a patient-centric approach in managing PTSD.
The Role and Limitations of Clinical Practice Guidelines
Clinical practice guidelines serve as a vital framework for diagnosing and treating PTSD; however, they are not prescriptive "cookbook" manuals. Instead, they offer broad recommendations and parameters to guide clinicians in managing this often underdiagnosed and undertreated condition. Several reputable guidelines exist, such as those developed by Veterans Affairs (VA)/Department of Defense, the International Society for Traumatic Stress Studies (ISTSS), and the American Psychiatric Association (APA). These guidelines emphasize the need for awareness and screening of PTSD, especially in patients who have experienced traumatic events.
A critical starting point is recognizing the core domains of PTSD: intrusive thoughts, autonomic hyperarousal and startle responses, avoidant behaviors, and mood and cognitive symptoms.1 Screening tools, such as the CAPS-5 (Clinician-Administered PTSD Scale for DSM-5), can assist clinicians in identifying and assessing the severity of PTSD symptoms.2 These guidelines also highlight the importance of distinguishing between trauma exposure and the actual development of PTSD. PTSD is an abnormal response to a severe trauma, and in fact most people exposed to severe trauma do not develop PTSD.
FDA-Approved Treatments for PTSD
Currently, only two medications have received FDA approval for the treatment of PTSD: sertraline and paroxetine, both of which belong to the class of selective serotonin reuptake inhibitors (SSRIs).3 Despite their established efficacy, these medications were approved over two decades ago and have limitations:
- Effectiveness Across Symptom Dimensions: These SSRIs can improve overall PTSD symptoms but often have a modest impact, particularly in certain symptom clusters. For example, they may not be as effective in treating avoidance symptoms, which are a critical component of PTSD.4,5
- Old Diagnostic Framework: Sertraline and paroxetine were developed based on older definitions of PTSD that did not include the more recent DSM-5 criteria, such as disturbances in mood and cognition. As a result, their efficacy may be limited when addressing the full spectrum of PTSD symptoms.4,5
While sertraline and paroxetine remain foundational treatments, there is a need for more comprehensive, targeted therapies that can address the nuanced symptomatology of PTSD, especially in women.
Off-Label and Emerging Treatments
Given the limitations of on-label medications, clinicians often resort to off-label treatments to manage PTSD symptoms more effectively. These off-label treatments include:
- SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors): Venlafaxine has shown some efficacy in treating PTSD and is acknowledged in practice guidelines, although it is not FDA-approved for this indication.6
- Atypical Antipsychotics: These have a long history of off-label use in PTSD management, with varying degrees of success. Quetiapine and newer agents like brexpiprazole have demonstrated some efficacy in treating hypervigilance, arousal, and intrusive thoughts. Notably, brexpiprazole has shown promising results in augmenting the effects of sertraline, especially in large, randomized trials where it achieved significant effect sizes. However, more research is needed to understand their role fully.7
- Alpha-Adrenergic Agents: Alpha-1 blocking medications such as prazosin have been used to address nightmares and flashbacks, but the data supporting their efficacy is mixed. Similarly, alpha-agonists like clonidine and guanfacine have been employed to manage hypervigilance and the fight-or-flight response, but their impact remains inconsistent.8,9
- Psychedelic-Assisted Therapy: There is growing interest in psychedelic medications such as MDMA (3,4-methylenedioxymethamphetamine) and psilocybin as adjuncts to psychotherapy for PTSD. MDMA, in particular, has shown potential in facilitating trauma processing and extinction of aversive responses in therapy. However, its approval has been delayed due to concerns about study methodologies, such as the lack of diverse patient samples and inadequate blinding. The FDA has requested additional studies before making a final decision.10
- NMDA Receptor Antagonists: Medications like ketamine and investigational agents such as NYX-783 have shown promise in treating PTSD, and are notable due to their rapid action and potential to enhance neuroplasticity.11
- Other Emerging Treatments: There are ongoing studies exploring the potential of drugs targeting various neural pathways, such as fatty acid amide hydrolase (FAAH) inhibitors, alpha-7 nicotinic cholinergic receptor modulators, and other glutamate-targeting agents. These treatments hold the promise of addressing PTSD through mechanisms beyond traditional monoaminergic pathways.12,13
Behavioral Interventions and the Importance of Combination Therapy
Despite the availability of pharmacological options, behavioral interventions remain the cornerstone of PTSD treatment. Trauma-focused Cognitive Behavioral Therapy (CBT) and Eye Movement Desensitization and Reprocessing (EMDR) are well-established, evidence-based approaches that have demonstrated efficacy in helping patients process trauma and reduce PTSD symptoms. Guidelines consistently emphasize that these interventions should be considered first-line treatments, either alone or in combination with pharmacotherapy.14
Given the modest efficacy of existing pharmacological treatments, combining them with behavioral therapy offers a more comprehensive approach, potentially leading to improved outcomes. The integration of novel agents, such as brexpiprazole, with psychotherapy may offer more significant benefits by enhancing neuroplasticity and facilitating trauma processing.
Challenges in Treatment Adherence and Optimal Management
Adherence to treatment guidelines is crucial for achieving optimal outcomes in PTSD management. However, several challenges can hinder this process, including:
- Variability in Symptom Presentation: PTSD is a heterogeneous condition, and patients may present with diverse symptoms that can mimic or overlap with other psychiatric disorders. This variability necessitates individualized treatment approaches rather than a one-size-fits-all strategy.15
- Suboptimal Response to Treatment: Many patients experience only partial relief of symptoms with first-line treatments, leading to frustration and discontinuation. It is essential for clinicians to persevere and explore alternative or combination treatments, in order to ensure that patients receive comprehensive and personalized care.16
- The Need for Patient-Centric Care: Engaging patients in shared decision-making and maintaining an empathetic, patient-centered approach can enhance treatment adherence. Educating patients about the potential benefits and limitations of different treatment options, including off-label and emerging therapies, can foster a sense of hope and empowerment.17
The Future of PTSD Treatment: Mechanism-Based Therapies
The future of PTSD treatment lies in identifying and targeting the underlying neurobiological mechanisms that drive the condition. The following are areas in which this future is unfolding.
- Brexpiprazole: Brexpiprazole's ability to modulate multiple neurotransmitter systems, including serotonin, dopamine, and norepinephrine, makes it particularly suited for addressing the diverse and overlapping symptom domains of PTSD, such as mood disturbances, anxiety, hypervigilance, and cognitive dysfunction. Its recent success when used in combination with sertraline in clinical trials, demonstrating significant improvements in PTSD symptoms, suggests that brexpiprazole may offer a promising adjunctive treatment for patients who do not respond adequately to SSRIs alone, thereby providing a more comprehensive approach to symptom management.7
- Psychedelics and NMDA Modulation: The potential of MDMA and psilocybin to induce neuroplasticity and facilitate trauma processing is a groundbreaking area of research. These agents may help those with PTSD "relearn" and extinguish maladaptive fear responses, offering a novel mechanism of action compared to traditional treatments.10
- Novel Pathways: Targeting pathways involved in cellular reactivity, neurogenesis, and synaptic plasticity holds promise for developing treatments that can address the core pathology of PTSD rather than just alleviating symptoms.
Conclusion
Managing PTSD in women requires a nuanced, comprehensive approach that integrates evidence-based treatments, emerging therapies, and patient-centered care. While current guidelines provide a valuable framework, clinicians must remain flexible and open to new treatment possibilities, particularly given the complex and evolving nature of PTSD. The combination of pharmacological and behavioral interventions, guided by empathy and shared decision-making, offers the most promising path toward improving outcomes for women affected by this debilitating condition.
As research continues to advance, the development of mechanism-based therapies holds the potential to revolutionize PTSD treatment, providing more targeted and effective options that address the root causes of the disorder. Until then, clinicians should remain vigilant, compassionate, and committed to delivering high-quality care to women living with PTSD.
References
- National Institute of Mental Health. Post-Traumatic Stress Disorder (PTSD). https://www.nimh.nih.gov/health/statistics/post-traumatic-stress-disorder-ptsd
- Weathers FW, et al. The Clinician-Administered PTSD Scale for DSM–5 (CAPS-5): development and initial psychometric evaluation in military veterans. Psychol Assess. 2018;30(3):383-395.
- Williams T, Phillips NJ, Stein DJ, Ipser JC. Pharmacotherapy for post traumatic stress disorder (PTSD). Cochrane Database Syst Rev. 2022;3(3):CD002795.
- Martin A, Naunton M, Kosari S, Peterson G, Thomas J, Christenson JK. Treatment guidelines for PTSD: a systematic review. J Clin Med. 2021;10(18):4175.
- Huang ZD, Zhao YF, Li S, et al. Comparative efficacy and acceptability of pharmaceutical management for adults with post-traumatic stress disorder: a systematic review and meta-analysis. Front Pharmacol. 2020;11:559.
- Bajor LA, Balsara C, Osser DN. An evidence-based approach to psychopharmacology for posttraumatic stress disorder (PTSD) - 2022 update. Psychiatry Res. 2022;317:114840.
- O'Connor M. Adjunctive therapy with brexpiprazole improves treatment resistant complex post traumatic stress disorder in domestic family violence victims. Australas Psychiatry. 2020;28(3):264-266.
- Belkin MR, Schwartz TL. Alpha-2 receptor agonists for the treatment of posttraumatic stress disorder. Drugs Context. 2015;4:212286.
- Khalid S, Mitchell S, Al-Mateen C. Comparison of alpha-2 agonist versus alpha-1 antagonist for post-traumatic stress disorder-associated nightmares in pediatric patients. Ment Health Clin. 2024;14(3):199-203.
- Elsouri KN, Kalhori S, Colunge D, et al. Psychoactive drugs in the management of post traumatic stress disorder: a promising new horizon. Cureus. 2022;14(5):e25235.
- Varker T, Watson L, Gibson K, Forbes D, O'Donnell ML. Efficacy of psychoactive drugs for the treatment of posttraumatic stress disorder: a systematic review of MDMA, ketamine, LSD and psilocybin. J Psychoactive Drugs. 2021;53(1):85-95.
- Liu H, Zhang X, Shi P, et al. α7 nicotinic acetylcholine receptor: a key receptor in the cholinergic anti-inflammatory pathway exerting an antidepressant effect. J Neuroinflammation. 2023;20(1):84.
- Mayo LM, Rabinak CA, Hill MN, Heilig M. Targeting the endocannabinoid system in the treatment of posttraumatic stress disorder: a promising case of preclinical-clinical translation? Biol Psychiatry. 2022;91(3):262-272.
- Kar N. Cognitive behavioral therapy for the treatment of post-traumatic stress disorder: a review. Neuropsychiatr Dis Treat. 2011;7:167-181.
- Gros DF, Price M, Magruder KM, Frueh BC. Symptom overlap in posttraumatic stress disorder and major depression. Psychiatry Res. 2012;196(2-3):267-270.
- Fonzo GA, Federchenco V, Lara A. Predicting and managing treatment non-response in posttraumatic stress disorder. Curr Treat Options Psychiatry. 2020;7(2):70-87.
- National Academies of Sciences, Engineering, and Medicine. Delivering Patient-Centered Trauma Care. In: Berwick D, Downey A, Cornett E, eds. A National Trauma Care System: Integrating Military and Civilian Trauma Systems to Achieve Zero Preventable Deaths After Injury. The National Academies Press;2016.
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Overview
Disclosure of Relevant Financial Relationships
In accordance with the ACCME Standards for Integrity and Independence, Global Learning Collaborative (GLC) requires that individuals in a position to control the content of an educational activity disclose all relevant financial relationships with any ineligible company. GLC mitigates all conflicts of interest to ensure independence, objectivity, balance, and scientific rigor in all its educational programs.
Faculty:
Joseph F. Goldberg, MD
Clinical Professor of Psychiatry
Icahn School of Medicine at Mount Sinai
New York, NYDr. Goldberg has reported the following relevant financial relationships or relationships with ineligible companies of any amount during the past 24 months:
Receives royalties: American Psychiatric Publishing, Cambridge University Press?
Consulting Fees: AbbVie, Alkermes, Axsome, BioXcel, Intra-Cellular Therapies, Neumora, Neurelis, Otsuka, Sage Pharmaceuticals Sunovion, SupernusReviewers/Content Planners/Authors:
- Cindy Davidson has nothing to disclose.
- Barry A. Fiedel, PhD, has nothing to disclose.
- Brian P. McDonough, MD, FAAFP, has nothing to disclose.
Learning Objectives
After participating in this educational activity, participants should be better able to:
- Evaluate the inadequacies and risks associated with off-label treatments for post-traumatic stress disorder (PTSD)
- Explain the link between the pathophysiology of PTSD and the pharmacological rationale for treatment
- Demonstrate knowledge of new and emerging therapies and how they fit into the clinical management of PTSD
Target Audience
This activity has been designed to meet the educational needs of pyschiatrists and primary care physicians, as well as all other physicians, physician assistants, nurse practitioners, nurses, pharmacists, and healthcare providers involved in managing patients with post-traumatic stress disorder (PTSD).
Accreditation and Credit Designation Statements
In support of improving patient care, Global Learning Collaborative (GLC) is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC) to provide continuing education for the healthcare team.
Global Learning Collaborative (GLC) designates this enduring activity for a maximum of .25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Global Learning Collaborative (GLC) designates this activity for .25 nursing contact hours. Nurses should claim only the credit commensurate with the extent of their participation in the activity.
Global Learning Collaborative (GLC) has been authorized by the American Academy of PAs (AAPA) to award AAPA Category 1 CME credit for activities planned in accordance with AAPA CME Criteria. This activity is designated for .25 AAPA Category 1 CME credits. Approval is valid until November 15, 2025. PAs should claim only the credit commensurate with the extent of their participation in the activity.
Global Learning Collaborative (GLC) designates this activity for .25 contact hours/.025 CEUs of pharmacy contact hours.
The Universal Activity Number for this program is JA0006235-0000-24-128-H01-P. This learning activity is knowledge-based. Your CE credits will be electronically submitted to the NABP upon successful completion of the activity. Pharmacists with questions can contact NABP customer service (custserv@nabp.net).Provider(s)/Educational Partner(s)
It’s about time! Today’s on-the-go learners have minutes to spend on education instead of hours. Total CME is an award-winning, global healthcare education company that strategically pioneers methodology, initiatives, and platforms to meet these time-limited needs. Unlike other medical education companies, Total CME employs a microlearning approach and platform to create outcome-based curricula that motivates HCPs to engage in self-directed point-of-care learning that impacts change in real time. Even while reaching the largest global distribution, we provide the most personalized, seamless learner experience. We’re meeting our busy learners where they are so they can focus on what they want when they need it, ultimately leading to behavior changes that impact clinical practice and empower patients in their own care.Commercial Support
This activity is supported by an independent educational grant from Otsuka America Pharmaceutical Inc. and Lundbeck, Inc.
Disclaimer
The views and opinions expressed in this educational activity are those of the faculty and do not necessarily represent the views of GLC and Total CME, LLC. This presentation is not intended to define an exclusive course of patient management; the participant should use his/her clinical judgment, knowledge, experience, and diagnostic skills in applying or adopting for professional use any of the information provided herein. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients’ conditions and contraindications or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities. Links to other sites may be provided as additional sources of information. Once you elect to access a site outside of Total CME, LLC you are subject to the terms and conditions of use, including copyright and licensing restriction, of that site.
Reproduction Prohibited
Reproduction of this material is not permitted without written permission from the copyrightSystem Requirements
- Supported Browsers (2 most recent versions):
- Google Chrome for Windows, Mac OS, iOS, and Android
- Apple Safari for Mac OS and iOS
- Mozilla Firefox for Windows, Mac OS, iOS, and Android
- Microsoft Edge for Windows
- Recommended Internet Speed: 5Mbps+
Publication Dates
Release Date:
Expiration Date:
Overview
The current FDA-approved drugs to treat post-traumatic stress disorder (PTSD) are often only minimally effective in clinical practice. One response is the frequent use of off-label drugs in the hope of improving the quality of life of patients impacted by PTSD. This approach often comes with adverse consequences for patients and with little improvement in their quality of life. But the treatment landscape for PTSD may change for the better with the emergence of a number of investigative agents. Join Drs. Joseph Goldberg and Roger McIntyre as they evaluate the value proposition of both current PTSD treatments and those in clinical trials.
Disclosure of Relevant Financial Relationships
In accordance with the ACCME Standards for Integrity and Independence, Global Learning Collaborative (GLC) requires that individuals in a position to control the content of an educational activity disclose all relevant financial relationships with any ineligible company. GLC mitigates all conflicts of interest to ensure independence, objectivity, balance, and scientific rigor in all its educational programs.
Faculty:
Joseph F. Goldberg, MD
Clinical Professor of Psychiatry
Icahn School of Medicine at Mount Sinai
New York, NYDr. Goldberg has reported the following relevant financial relationships or relationships with ineligible companies of any amount during the past 24 months:
Receives royalties: American Psychiatric Publishing, Cambridge University Press?
Consulting Fees: AbbVie, Alkermes, Axsome, BioXcel, Intra-Cellular Therapies, Neumora, Neurelis, Otsuka, Sage Pharmaceuticals Sunovion, SupernusReviewers/Content Planners/Authors:
- Cindy Davidson has nothing to disclose.
- Barry A. Fiedel, PhD, has nothing to disclose.
- Brian P. McDonough, MD, FAAFP, has nothing to disclose.
Learning Objectives
After participating in this educational activity, participants should be better able to:
- Evaluate the inadequacies and risks associated with off-label treatments for post-traumatic stress disorder (PTSD)
- Explain the link between the pathophysiology of PTSD and the pharmacological rationale for treatment
- Demonstrate knowledge of new and emerging therapies and how they fit into the clinical management of PTSD
Target Audience
This activity has been designed to meet the educational needs of pyschiatrists and primary care physicians, as well as all other physicians, physician assistants, nurse practitioners, nurses, pharmacists, and healthcare providers involved in managing patients with post-traumatic stress disorder (PTSD).
Accreditation and Credit Designation Statements
In support of improving patient care, Global Learning Collaborative (GLC) is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC) to provide continuing education for the healthcare team.
Global Learning Collaborative (GLC) designates this enduring activity for a maximum of .25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Global Learning Collaborative (GLC) designates this activity for .25 nursing contact hours. Nurses should claim only the credit commensurate with the extent of their participation in the activity.
Global Learning Collaborative (GLC) has been authorized by the American Academy of PAs (AAPA) to award AAPA Category 1 CME credit for activities planned in accordance with AAPA CME Criteria. This activity is designated for .25 AAPA Category 1 CME credits. Approval is valid until November 15, 2025. PAs should claim only the credit commensurate with the extent of their participation in the activity.
Global Learning Collaborative (GLC) designates this activity for .25 contact hours/.025 CEUs of pharmacy contact hours.
The Universal Activity Number for this program is JA0006235-0000-24-128-H01-P. This learning activity is knowledge-based. Your CE credits will be electronically submitted to the NABP upon successful completion of the activity. Pharmacists with questions can contact NABP customer service (custserv@nabp.net).Provider(s)/Educational Partner(s)
It’s about time! Today’s on-the-go learners have minutes to spend on education instead of hours. Total CME is an award-winning, global healthcare education company that strategically pioneers methodology, initiatives, and platforms to meet these time-limited needs. Unlike other medical education companies, Total CME employs a microlearning approach and platform to create outcome-based curricula that motivates HCPs to engage in self-directed point-of-care learning that impacts change in real time. Even while reaching the largest global distribution, we provide the most personalized, seamless learner experience. We’re meeting our busy learners where they are so they can focus on what they want when they need it, ultimately leading to behavior changes that impact clinical practice and empower patients in their own care.Commercial Support
This activity is supported by an independent educational grant from Otsuka America Pharmaceutical Inc. and Lundbeck, Inc.
Disclaimer
The views and opinions expressed in this educational activity are those of the faculty and do not necessarily represent the views of GLC and Total CME, LLC. This presentation is not intended to define an exclusive course of patient management; the participant should use his/her clinical judgment, knowledge, experience, and diagnostic skills in applying or adopting for professional use any of the information provided herein. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients’ conditions and contraindications or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities. Links to other sites may be provided as additional sources of information. Once you elect to access a site outside of Total CME, LLC you are subject to the terms and conditions of use, including copyright and licensing restriction, of that site.
Reproduction Prohibited
Reproduction of this material is not permitted without written permission from the copyrightSystem Requirements
- Supported Browsers (2 most recent versions):
- Google Chrome for Windows, Mac OS, iOS, and Android
- Apple Safari for Mac OS and iOS
- Mozilla Firefox for Windows, Mac OS, iOS, and Android
- Microsoft Edge for Windows
- Recommended Internet Speed: 5Mbps+
Publication Dates
Release Date:
Expiration Date:
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